Pericytes and Lung Vascular Remodeling

Pericytes are mural cells that line capillaries throughout the brain, retina, lung, and other organs, where they support capillary homeostasis through direct contact and paracrine crosstalk with capillary endothelium. Despite being described more than a century ago, their contributions to health and vascular diseases remain unclear, largely due to the difficulty of definitive identification. Their inherent plasticity, as well as shared markers and close lineage relationships with other mural cells, results in overlap in identification and underrepresentation in single-cell data sets. Emerging evidence reveals that pericytes play a critical role in the vascular remodeling characteristics of pulmonary hypertension, via mechanisms involving smooth muscle-like phenotypic switching and morphological changes influenced by hypoxia signaling, transforming growth factor-β, cyclic GMP modulation, and disrupted pericyte-endothelial communication. Recent single-cell RNA sequencing enabled the identification of a novel and specific pericyte marker, Higd1b, thereby improving pericyte identification and revealing novel pericyte subtypes. In this review, we summarize historical and recent insights into pericyte morphology and function, their increasingly recognized role in pulmonary hypertension pathobiology, and the potential to unlock novel therapeutic avenues targeting pericytes.